Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats

Schoenle, Eugen J.; Zapf, J.; Hauri, C; Steiner, Therese; Froesch, E. R.

doi:10.1530/acta.0.1080167

Cited by 190 publications

(88 citation statements)

References 13 publications

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“…In hypophysectomized rats IGF-II administration promotes growth although less well than IGF-I (Schoenle et al 1985, Shaar et al 1989, Conlon et al 1995. Similar results were obtained in Pit-1-deficient Snell dwarf mice (van Buul-Offers et al 1988.…”

Section: Introductionsupporting

confidence: 76%

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

Rooman¹,

Köster²,

Bloemen³

et al. 1999

Journal of Endocrinology

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The physiological role of IGF-II remains unclear but there is evidence for a role in postnatal growth, the growth of the thymus and bone homeostasis. Glucocorticoids have many effects that are opposite to the effects of IGF-II such as growth retardation, osteoporosis and thymic involution. We therefore wondered whether IGF-II overexpression in transgenic mice might counteract some of the growth inhibitory effects of the glucocorticoid, dexamethasone (DXM).In a dose-finding study in normal mice, 20 µg DXM/ day caused a significant growth delay. The various organs had a different susceptibility to the growth inhibitory effects of DXM. Most affected were thymus and spleen, followed by liver, skeletal muscle and lumbar vertebrae. The weights of the kidney, tibia, and humerus were not significantly diminished.In a second experiment, the effects of DXM in normal and IGF-II-transgenic animals were compared. The IGF-II serum levels in the transgenic animals were more than 40-fold increased compared with control mice and were decreased by 35% in the DXM-treated group. IGF-I serum levels were identical in both mouse strains and rose slightly after DXM administration in controls. Transgenic mice had higher levels of IGF binding protein species of apparent molecular masses of 41·5 kDa, 30 kDa, and 26·5 kDa. DXM reduced the 24 kDa band in both mice strains. In addition it reduced the bands at 38·5 kDa and 26·5 kDa but only in the transgenic animals.The effect of DXM on body growth was similar in normal and IGF-II-transgenic mice. The weight reduction of the various organs caused by DXM was similar in both types of mice except for the skeleton. The weight of the tibia and the humerus were significantly higher in the DXM-treated transgenic mice.In conclusion, we speculate that overexpression of IGF-II in mice partially protects bone from the osteopenic effects of glucocorticoids.

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Section: Introductionsupporting

confidence: 76%

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

Rooman¹,

Köster²,

Bloemen³

et al. 1999

Journal of Endocrinology

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“…Recently, hypophysectomised rats were infused with pure insulin-like growth factor I or II, and somatic growth was augmented in a dose dependent manner [23,24]. Others have observed no effect or only a slight increase in skeletal growth when hypophysectomised rats or hypopituitary dwarf mice were treated with crude somatomedin preparations or recombinant methionyl insulin-like growth factor I [25][26][27]. In the present study, the subcutanous injection of growth hormone increased body length, the width of the tibia growth plate, and the incorporation of sulfate into rib cartilage.…”

Section: Discussionmentioning

confidence: 99%

Insulin stimulates skeletal growth in vivo and in vitro ?? comparison with growth hormone in rats

1989

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Summary. The effect of insulin on skeletal growth was examined by (1) systemic injection, (2) local administration into the tibia growth plate and (3) in vitro by use of chondrocytes in culture.(1) Male rats, body weight 60-75 g, were hypophysectomised. One week after the operation, the animals were divided into three groups. Group A received intraperitoneally saline, group B insulin (5-30 U. kg-1. day-1) and group C human growth hormone (250 txg/kg/day) for the following 10 days. In addition, on day 10 the rats were injected with 10 txCi 35-S-sulfate intraperitoneally. Twenty-four h later in the non-fasting state plasma glucose, insulin, somatomedin activity (porcine assay), body weight, nose-rump length, width of the tibia growth plate, and the 35-S-sulfate incorporation into rib cartilage were determined. Compared to saline, growth hormone and insulin treatment significantly enhanced body weights, nose-rumb lengths, the widths of the proximal tibia growth plates and the incorporation of sulfate into rib cartilage. For the three skeletal growth parameters, growth hormone was more effective than insulin, while body weights did not differ after insulin or growth hormone treatment. Somatomedin activity (U/ml) was low in group A (0.39 + 0.04, n = 9, Mean + SEM) and group B (0.34 + 0.08, n = 8) and high in the growth hormone treated group C (0.90+0.09, n=7; p < 0.002). (2) To test the possibility that insulin might directly augment skeletal growth, insulin (80 mU) was injected into the proximal tibia growth plate of one leg and saline into the cartilage zone of the other leg. Insulin treatment significantly increased the width of the cartilage zones. Insulin: 211 + 22 ~m, saline 200 + 22 ]xm, (Mean + SD, n = 6, p < 0.05). (3) Addition of human biosynthetic insulin and growth hormone to the culture medium increased colony formation of chondrocytes in a bell-shaped fashion. A plateau in colony formation was reached with 3.1-6.25 ng/ml insulin and 25-50 ng/ml growth hormone, but with larger dosages of both hormones, the effect was diminished. The results suggest that insulin might stimulate postnatal skeletal growth by a direct effect on the target cells.

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“…W natural serum 1; X serum 1 with addition of E 7-21 ; A natural serum 2; B serum 2 with addition of E [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] . % B ¼ percent bound.…”

Section: European Journal Of Endocrinology (1997) 137mentioning

confidence: 99%

“…Very high IGF-II gene expression patterns have been found in some tumors including central nervous system tumors (5,6) and in a large variety of tissues during fetal development (7)(8)(9). Although IGF-I is known to be the most important postnatal growth factor (10,11), circulating IGF-II levels in adult humans are higher than the equivalent IGF-I levels presumably originating from the P1 promoter in the liver (12). High IGF-II mRNA expression, especially in sarcomas and some common tumors in children such as Wilms' tumors (13), is evidence for an auto/paracrine function of IGF-II during malignant transformation and tumor development (14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

“…To sum up, 'big-IGF-II' of different molecular weights has been found in normal tissue, serum (27) or spinal fluid (28) and has also been isolated from tumor cell cultures in vitro, such as a colon carcinoma cell line (29), a teratocarcinoma cell line (30) or a rhabdomyosarcoma cell line (31), with molecular masses ranging from 10 to 16 kDa. Therefore we set out to measure pro-IGF-II, produced by Wilms' tumor cells and secreted into the medium, by a newly developed radioimmunoassay using an antibody directed against amino acids 7-21 of the E-domain of pro-IGF-II (E [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] ) and to determine the molecular weights of various pro-IGF-II forms by gel electrophoresis and immunoblotting with this antibody. prestained molecular weight standards and the goat antirabbit IgG-AP Immun-Lite Chemiluminescent Assay Kit were from Bio-Rad (Hercules, CA, USA).…”

Section: Introductionmentioning

confidence: 99%

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High molecular weight forms of IGF-II ('big-IGF-II') released by Wilms' tumor cells

Schmitt

Ren-Qiu²,

Torresani³

et al. 1997

European Journal of Endocrinology

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Insulin-like growth factor-II (IGF-II) is thought to play a critical role in the development of embryonic tumors such as Wilms' tumor. However, despite highly elevated IGF-II mRNA levels in tumors, IGF-II is not elevated in the serum of patients with Wilms' tumors. Recently high molecular weight forms of IGF-II ('big'-or pro-IGF-II) have been found to be produced by some tumors. In order to prove whether or not high molecular weight forms of IGF-II are produced by Wilms' tumor cells and secreted into the culture medium, we established Wilms' tumor cell lines. After column chromatography of the culture medium, IGF-II and pro-IGF-II concentrations were measured. For pro-IGF-II measurement we established a pro-IGF-II RIA using a rabbit polyclonal antiserum directed against amino acids 7-21 (E 7-21 ) of the E-domain of pro-IGF-II. Gel electrophoresis and Western blotting with anti-IGF-II antibodies revealed a band at 7.5 kDa corresponding to fully processed IGF-II and bands between 10 and 20 kDa. Using pro-IGF-II antiserum, bands between 10 and 25 kDa were detected. We conclude that in vitro cultured Wilms' tumor cells produce and release various forms of 'big IGF-II' with molecular masses between 10 and 25 kDa. It remains uncertain whether these high molecular weight forms of IGF-II represent normal precursors of IGF-II or incorrectly processed IGF-II.

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Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats

Cited by 190 publications

References 13 publications

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

Insulin stimulates skeletal growth in vivo and in vitro ?? comparison with growth hormone in rats

High molecular weight forms of IGF-II ('big-IGF-II') released by Wilms' tumor cells

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